Novel Drugs Demonstrate Benefits of Once Weekly Drugs for Weight Loss andGlycemic and Blood Pressure Control

ORLANDO, Fla., June 23, 2024 /PRNewswire/ -- Findings from three studies showcase new data on the latest developments in drug therapy innovations to treat obesity including new insights on GLP-1 (Glucagon-like peptide-1) receptor agonists. The data was presented as a late-breaking poster and oral presentations, respectively at the American Diabetes Association (ADA) 84th Scientific Sessions in Orlando, FL.

The studies are part of a host of research and development driven by interest in new GLP-1 drugs and concerns about obesity. Obesity affects about 125 million people in the United States 41.9% of adults and 19.7% of children and adolescents. Notably, 90% of people with diabetes also live with overweight or obesity. Weight gain is a major problem for physicians and patients looking to achieve adequate glycemic, blood pressure and lipid control in patients with diabetes.

"Over the past few years, we have seen the substantial impact of new research working to solve the dual health crisis we are facing, obesity and diabetes," said Dr. Robert Gabbay, chief scientific and medical officer for the ADA. "The studies we are seeing presented at this year's annual meeting show great promise to fuel new solutions and treatment options for patients across the globe living with type 2 diabetes and obesity."

Drug Treatment for Obesity Effectively Reduces Body Weightand Blood Pressure

HRS9531 is a dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) receptor agonist, offering a treatment option for individuals with overweight or obesity, as well as type 2 diabetes. This Phase 2 study evaluated the efficacy and safety of HRS9531 in obese adults without diabetes. The research found HRS9531 effectively reduced body weight, blood pressure, blood glucose, and triglycerides, with a favorable safety profile.

The double-blind, randomized, placebo-controlled Phase 2 trial studied a total of 249 Chinese adults with a body mass index of 28-40 kg/m. Participants were randomized into five groups to receive once-weekly subcutaneous injections of HRS9531 (1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg) or placebo for 24 weeks. The primary endpoint was the percentage change in body weight at week 24.

Greater weight loss was achieved in individuals receiving HRS9531 compared with those receiving placebo. At the end of the 24-week intervention, participants in 1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg HRS9531 groups achieved weight reductions of 5.4%, 13.4%, 14.0%, and 16.8% respectively, as compared with 0.1% reduction in the placebo group. Moreover, the proportion of participants achieving 5% weight reduction was 52.0%, 88.2%, 92.0%, 91.8%, and 10.2%, respectively. Most adverse events (AEs) were mild or moderate, and the most common AEs were nausea, diarrhea, decreased appetite, and vomiting, occurring primarily during dose escalation. The overall safety and tolerability profile of HRS9531 is consistent with other GLP-1 agonists.

"People living with obesity are at a high risk of developing chronic diseases such as type 2 diabetes and cardiovascular disease. Losing weight significantly reduces the risk of those diseases," said Xiaoying Li, MD, PhD. Professor and Director, Department of Endocrinology and Metabolism, Zhongshan Hospital Fudan University, China, and senior author. "Since dietary and exercise intervention alone is often not enough, we were pleased to see that this could be a potentially promising treatment for weight management, potentially enhancing their overall health and significantly reducing the societal burden of obesity."

The authors of the study note a Phase 3 study with HRS9531 in Chinese overweight or obese individuals is already ongoing and multi-regional studies are being planned.

Experimental Medication, Pemvidutide, Reveals 15.6% Average Total Body Weight Loss for Patients with Overweight and Obesity

The Phase 2 MOMENTUM trial evaluated the potential for pemvidutide, Altimmune's investigational medication, a GLP-1/Glucagon dual receptor agonist, in development for obesity and a liver disease called metabolic-dysfunction associated steatohepatitis (MASH), to help people with overweight and obesity lose weight. The trial revealed promising results - significantly reducing body weight and serum lipids over 48 weeks of treatment. In addition, body composition analysis demonstrated class-leading preservation of lean mass.

This Phase 2, randomized, placebo-controlled trial enrolled 391 subjects with overweight or obesity, but without diabetes, and administered either pemvidutide at three dose levels (1.2, 1.8, 2.4 mg) or a placebo weekly for 48 weeks. Neither the investigators nor the subjects knew what treatment they were receiving.

After 48 weeks, subjects at the highest pemvidutide dose had lost an average of 15.6% of their total body weight, and the treatment appeared to be safe and well-tolerated. Several potential advantages of this approach to weight loss were identified, including a simple dosing regimen and significant decreases in the amount of lipids (such as cholesterol and triglycerides) present in the blood and the liver, which may help reduce the risk of cardiovascular disease. Additionally, results from a body composition sub-study were presented indicating class-leading preservation of lean mass, with only 21.9% attributable to lean mass and 78.1% of weight loss due to fat. Preserving lean mass, which primarily includes muscle, is believed to be critical for maintaining physical function and decreasing the risk of bone fractures.

"Obesity and its associated comorbidities represent a major and growing health challenge. A variety of therapeutic approaches will be required to meet the specific needs of each patient to effectively manage their weight and address other obesity-related conditions they may have," said Louis J. Aronne, MD, FACP, DABOM, Weill Cornell Medicine, New York City, NY, and primary investigator. "These findings demonstrated that the use of pemvidutide may have important effects on the quality of weight loss and cardiometabolic-associated comorbidities of obesity. Furthermore, as the focus shifts to long-term weight management, the preservation of lean mass will be critical for patient care."

The authors of this study are preparing for larger Phase 3 registrational trials intended to demonstrate the safety and clinical benefit of pemvidutide for weight management. In addition, because obesity can lead to the accumulation of excess liver fat and MASH, they are also studying pemvidutide in patients with this condition.

Retatrutide Improves Ability of Insulin to Lower Blood Sugar for People Living with Type 2 Diabetes

Biomarker analyses may help in the understanding of diseases and identifying specific therapeutic targets. A new study evaluated biomarkers to observe how treatment with retatrutide affects pancreatic beta cells that make insulin as well as biomarkers associated with the body's ability to respond to insulin to lower blood sugar. In this study, exploratory biomarker research within phase 2 clinical trials was examined to further understand on the molecular level how retatrutide may work and further help explain primary results.

The research found treatment with retatrutide increased markers of well-functioning insulin-producing beta cells (HOMA2-B) and the ability of insulin to lower blood sugar (adiponectin). The results also demonstrated how retatrutide decreased markers of stress on insulin-producing cells, as assessed by measuring immature insulin (proinsulin) and reduction in a marker of insulin resistance (HOMA2-IR).

"This study matters because many people living with type 2 diabetes are taking multiple diabetes medications to try to reach blood sugar targets, and new medications that have the potential to help simplify treatment regimens are needed," said Melissa K. Thomas, MD, PhD, Vice President, Diabetes and Metabolic Research, Lilly Research Laboratories, Indianapolis, IN, and one of the investigators conducting the study. "We are encouraged to see that people living with either obesity or with type 2 diabetes in our clinical studies had lowered blood sugar and had improved responses to insulin."

Several Phase 3 clinical trials are underway studying retatrutide in people living with type 2 diabetes or obesity without type 2 diabetes including the TRIUMPH and TRANSCEND Phase 3 trials.

Research presentation details:

Dr.Zeng will present the findings at the following late-breaking poster session:

Dr. Aronne will present the findings at the following presentation session:

Dr. Thomas will present the findings at the following oral presentation session:

About the ADA's Scientific SessionsThe ADA's 84th Scientific Sessions, the world's largest scientific meeting focused on diabetes research, prevention, and care, will be held in Orlando, FL on June 21-24. More than 11,000 leading physicians, scientists, and health care professionals from around the world are expected to convene both in person and virtually to unveil cutting-edge research, treatment recommendations, and advances toward a cure for diabetes. Attendees will receive exclusive access to thousands of original research presentations and take part in provocative and engaging exchanges with leading diabetes experts. Join the Scientific Sessions conversation on social media using #ADAScientificSessions.

About the American Diabetes AssociationThe American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to bend the curve on the diabetes epidemic and help people living with diabetes thrive. For 83 years, the ADA has driven discovery and research to treat, manage, and prevent diabetes while working relentlessly for a cure. Through advocacy, program development, and education we aim to improve the quality of life for the over 136 million Americans living with diabetes or prediabetes. Diabetes has brought us together. What we do next will make us Connected for Life. To learn more or to get involved, visit us atdiabetes.orgor call 1-800-DIABETES (1-800-342-2383). Join the fight with us on Facebook (American Diabetes Association), Spanish Facebook (Asociacin Americana de la Diabetes), LinkedIn (American Diabetes Association), Twitter (@AmDiabetesAssn), and Instagram (@AmDiabetesAssn).

Media Contact: Amy Robinson [emailprotected]

SOURCE American Diabetes Association

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The American Diabetes Association Highlights Innovations in New Drug Therapies for Patients with Obesity - PR Newswire

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The relationship between SARS-CoV-2 infection and type 1 diabetes mellitus - Nature.com

A cross-sectional observational study was conducted on 225 patients (42.2% males and 57.8% females) with type I (2.2%) and type II DM (97.8%), having a diabetic history of fewer than five years in 56% of participants of age ranging from 35-70 years, The study aimed to scrutinize the prevalence of peripheral neuropathy and amputation in patients with DM and evaluate their quality of life by utilizing the Michigan Neuropathy Screening Instrument and the Asian Diabetic Quality of Life Questionnaire. The levels of amputation from toe amputations to hemipelvectomy were observed.

Martin CL et al. in 2014 found that the most common of these neuropathic disorders is chronic diabetic peripheral sensorimotor neuropathy (DPN), which affects up to 50% of persons with DM14. The study's findings revealed a significant prevalence of peripheral neuropathy among the participants, emphasizing the considerable burden of this complication in patients with DM. Our study conducted on 225 patients with DM demonstrates the prevalence of DNP (diabetic peripheral neuropathy) using the Michigan neuropathy screening instrument (MNSI) self-administer questionnaire (SAQ) was 44.4% and 51.1% on the basis of the lower extremity examination part of the MNSI. Whereas, 55.6% and 48.9% were observed for the population without DPN using SAQ and the physical examination part of MNSI, respectively. Peripheral neuropathy is a well-recognized consequence of DM, characterized by nerve damage that can lead to various sensory and motor deficits, including pain, tingling, numbness, loss of sensation, muscle weakness, and impaired balance. The high prevalence rate underscores the need for early detection and effective management strategies to prevent or mitigate its adverse effects on patients well-being.

Hazari et al. (2023) reported that the risk of DPN is ethnic origin-dependent in residents of the United Arab Emirates and is high in Arab-origin residents. According to the findings of MNSI, 62% of the participants were screened with DPN28. The current study's findings are in line with their results in terms of DPN on the basis of MNSI but are limited in terms of information regarding the ethnicity and geographical background of the participants.

Amputation, another severe complication associated with DM, was also found to be prevalent in the study sample. This outcome raises concerns about the impact of DM on vascular health and underscores the significance of comprehensive diabetic foot care programs. Amputations can have profound physical, psychological, and social implications for individuals, leading to long-term disability and reduced quality of life. The identification of factors such as age, duration of DM, and glycemic control as predictors of peripheral neuropathy and amputation provides valuable insights for risk stratification and targeted interventions. In this study, the prevalence of amputations observed in patients with DM in the right and left lower limb are 0.4% and 0% hemipelvectomy, respectively, with short above knee amputation being 0.4%, 2.2%, respectively, standard below the knee in 9.8%, 3.6% respectively, toe disarticulation or amputation in 2.7%, 1.8 respectively, and Symes being 0.4% in both lower limbs. Baumfeld D et al. in 2018 found that in Pakistan, the rate of amputation (number of amputations due to diabetes per year) has been reported to be 21%-48%, despite the prevalence of diabetic foot ulcerations that is comparable to that of other countries29. The total rate of amputation, according to our study among the sample population, is 21.7%, which is similar to other research done before.

Furthermore, the study demonstrated the quality of life of the participants. This finding highlights the multidimensional nature of quality of life and the significant impact that these complications have on various aspects of a patient's well-being. According to the results of our study, DPN and amputation may have a negative association with four components of Asian DQOL in patients with DM. Our study showed that 96.9% of the population had poor QOL (score<45), 2.2% had moderate QOL (score 4550), and 0.9% had good QOL (score 5055). The study concluded results for four components of the Asian DQOL questionnaire with lower scores indicating poor QOL and vice versa. Total energy score 83.6% with (scores of 04) 14.7%, and 1.8% (scores 58 and 912, respectively), total memory scores 04, 58, 912, and 1316 with 30.0%, 34.7%, 20.9%, and 14.2% respectively, total finance score 05, 610, 1115, and 1620 with 51.1%, 39.6%, 6.7%, and 2.7% respectively, and total diet score of 04, 58, 912 with 67.1%, 30.2%, and 2.7% respectively. The mean energy score is 2.811.82 out of 12, which seems to be very low; the mean memory score is 7.974.53 out of 16, appearing as less than half of the total score, mean finance score is 6.384.34 out of 20 which is also very poor, mean diet score is 3.772.17 out of 12 and total score is 20.9510.40 out of 60. Most of the results depict poor quality of life in the study population.

Physical functioning is often compromised due to the sensory and motor deficits associated with peripheral neuropathy, limiting mobility and impairing daily activities. Psychological well-being is affected by chronic pain, anxiety, depression, and the psychological adjustment to the loss of a limb in the case of amputation. Social interactions may also be impacted as individuals may experience social stigma, reduced participation in social activities, and a sense of isolation. Overall, life satisfaction is significantly diminished as a result of the limitations imposed by these complications. According to our findings, numerous studies from different countries have indicated that type II DM has a detrimental effect on QOL30,31,32,33.

While this study provides valuable insights into the prevalence of peripheral neuropathy, amputation, and quality of life in patients with DM, it is important to acknowledge certain limitations. The cross-sectional design of this study limits the ability to establish causal relationships between variables. Longitudinal studies would be beneficial in determining temporal relationships and understanding the long-term effects of these complications.

Healthcare providers should prioritize early detection and screening of peripheral neuropathy in patients with Diabetic mellitus. A multidisciplinary approach involving healthcare professionals from various specialities, such as endocrinology, podiatry, and physical therapy, is recommended, along with long-term follow-up. Collaboration among these specialists can provide comprehensive care, including education, foot care guidance, wound management, and rehabilitation services for individuals with peripheral neuropathy or amputation. Recognizing the impact of peripheral neuropathy and amputation on the quality of life, healthcare providers should offer psychological support and rehabilitation services to affected patients. Access to counselling, prosthetics and mobility aids can help individuals cope with the physical, emotional, and social challenges associated with these complications.

The present study had a few limitations which need to be mentioned here. The study's sample was drawn from patients attending a specific healthcare facility, which may introduce sampling bias and limit the generalizability of the findings to a broader population. Patients seeking care at these facilities may have different characteristics or access to healthcare compared to the general population. Individuals with concurrent chronic illnesses like heart disease, cancer, or renal disorders, with a history of trauma, severe psychiatric conditions, or addiction were excluded due to some ethical limitation. This prevented the analysis from having external validity. Many patients have multiple comorbidities, and it is difficult for neuropathy to be the only complication.

Only MNSI was used, and it could not be compared with nerve conduction study, which is a gold standard for diagnosing patients with peripheral neuropathy. Due to ethical considerations, the interpersonal relationship component of Asian DQOL was not included in this study. The study relied on self-reported data, which was subjected to recall bias. Patients may have inaccurately reported their medical history, symptoms, or quality of life. Additionally, subjective assessments of QoL may be influenced by individual perceptions and experiences.

More:
Prevalence of peripheral neuropathy, amputation, and quality of life in patients with diabetes mellitus | Scientific Reports - Nature.com

Despite medical cannabis in the US dating back more than 3 decades, the legalization movement in the last decade means millions and millions of US adults now have access to cannabis, for both medical and recreational purposes.

However, with this boom in use, concerns regarding the health effects of cannabis use have become a greater focal point of discussion among medical circles. According to a 2023 study in JAMA Network Open, 17% of a 175,000-patient cohort of adults reported cannabis use in the previous 3 months and 34.7% of those individuals met the criteria for moderate to high risk for cannabis use disorder.1

At the 84th American Diabetes Association Scientific Sessions, Halis Akturk, MD, associate professor of medicine and pediatrics at the Barbara Davis Center for Diabetes at the University of Colorado, led a session titled The Highs and Lows of Cannabis Use in DiabetesBehavioral and Psychosocial Considerations. Based in Colorado, Akturk has a unique view from the frontlines of research and real-world practice as Colorado was among the first states to allow for both medical and nonmedical cannabis use.

In the past 5 years, Akturk has published numerous studies detailing the effects of cannabis use with type 1 diabetes. In 2019, a study from Akturk in JAMA Internal Medicine evidenced the elevated risk of diabetic ketoacidosis among adults with type 1 diabetes using cannabis receiving care at the Barbara Davis Center for Diabetes. Building o this research, a similar study published in Diabetes Care in 2020 confirmed a similar trend using data from the T1D Exchange clinical registry. In 2022, Akturk led an additional study providing clinicians with an overview of the differences in presentation between diabetic ketoacidosis and hyperglycemic ketosis due to cannabis hyperemesis syndrome.2,3,4

At ADA 2024, we sat down with Akturk to learn more about this emerging space, what additional risks are associated with cannabis use in adults with and without type 1 diabetes, and what questions hears most often from his colleague regarding the topic.

HCPLive: What is the prevalence of cannabis use among people with type 1 diabetes and what are the primary reasons cited for use?

Akturk: In Colorado, we have the one of the highest rates of cannabis users with type one diabetes. So, we did a survey study a couple years ago and we asked the adults with type one diabetes: "Have you been using the cannabis or have you ever used the cannabis in the last 12 months?". In the results, there were about 30% of the patients in the adult clinic with type 1 diabetes that were at least used once cannabis in the last one year. The reasons for use were multiple, with about 75% of the people were using recreational reasons and 25% of the people were using medicinal reasons. In some states, you can just get a medicinal card for different indications. This was relatively a high use in our community for type 1 diabetes.

HCPLive: What are some of the chief concerns about how the effects of cannabis use manifest among patients with type 1 diabetes?

Akturk: Our previous research showed that the people who are using cannabis have an increased risk for diabetic ketoacidosis when they have type 1 diabetes. This was a local study we did a couple of years ago in JAMA, where we were trying to find out the reasons for that. Then we went to the T1D Exchange data and we looked to see if we can confirm our study results. We confirmed that the people who are using cannabis, after adjustment for the other things like pump use, age, diabetes, duration and other confounders, were at an increased for diabetic ketoacidosis.

As a next step, we realized that these people have a different the metabolic profile when they present to ER with the diabetic ketoacidosis symptoms. In other research, what we did is we looked at their metabolic profiles and their labs to compared people who are using cannabis and not using it. So, we did an objective study, and we looked at their urine drug screen use. If somebody's urine drug screen is positive for cannabis, we consider this person is using and, if it's not that, we consider that as not using it.

We found very significant differences in terms of the labs at presentation. We showed that these same people are also getting hyperglycemia, they are getting ketosis, and they have an onion gap. They also present to the ER with nausea and vomiting. But the main difference was the pH and the bicarb. So, their pH was more than 7.4 and their bicarb was more than 15. So, in DKA, there should be pH should be less than 7.3 and bicarb should be less than 15. So, we call them as a different entity, as hyperglycemic ketosis related to the cannabis hyperemesis syndrome.

HCPLive: When should providers approach discussions around cannabis use among patients with type 1 diabetes?

Akturk: I think we should educate people about cannabis at the type 1 diabetes diagnosis. We have a structured plan for the sick day management for alcohol and we added structures for cannabis education in the type 1 diabetes care program at the Barbara Davis Center. If there is a new patient, I suggest the providers, especially the endocrinologist, to discuss the cannabis with them at their first visit. If they have some frequent visits related to the ER visits and there are some frequent diabetic ketosis episodes, I suggest asking them if they use cannabis or not.

Editor's note: these transcripts have been edited for length and clarity.

Disclosures of interest for Akturk include REMD, Dexcom, Senseonics, and Eli Lilly and Company.

References:

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What to Know About Cannabis Use and Diabetes, with Halis Akturk, MD - MD Magazine

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Exploratory risk prediction of type II diabetes with isolation forests and novel biomarkers | Scientific Reports - Nature.com

By: Staff Writer | June 21, 2024 | 5 min. read| Share Article Summary

The Diabetes Research Institute (DRI) at the University of Miami Miller School of Medicine unveiled an innovative approach at the American Diabetes Associations (ADA) 84th Scientific Sessions that highlights the potential of human, stem cell-derived islets combined with an immunomodulatory microgel to reverse Type 1 diabetes (T1D).

This technology was developed to enable pancreatic islet cell replacement in the allogeneic setting (from a donor to an unrelated recipient) without the need for chronic, systemic immunosuppression.

The collaborative effort was spearheaded by Giacomo Lanzoni, Ph.D., a Miller School research assistant professor in biochemistry and molecular biology, with teams from iTolerance, Inc., and Kadimastem, Ltd. The research demonstrates that the combination of iTOL-100 engineered microgel developed by iTolerance, Inc., and IsletRx stem cell-derived islets developed by Kadimastem, Ltd., can effectively restore normoglycemia in a model of diabetes.

Our observations highlight the transformative potential of combining stem cell-derived islets with an immunomodulatory microgel, Dr. Lanzoni said. This approach could enable transplantation across the allogeneic barrier, offering a scalable and sustainable solution for T1D, and could enhance the safety and long-term efficacy of islet cell transplantation.

The Fast Track Center for Testing at the DRI Cell Transplant Center continues to serve as a key shared resource to validate emerging technologies towards a cure for diabetes, said Camillo Ricordi, M.D., director of the Cell Transplant Center and director emeritus at the Diabetes Research Institute as well as chief in the Division of Cellular Transplantation at the Miller School. We hope to continue to be of assistance towards the identification of reliable and potentially unlimited stem cell-derived islet sources for transplantation, which may one day be able to replace the limited availability of pancreas-derived islets from multiorgan donors, when lifelong recipient immunosuppression will no longer be required.

The studys key findings indicate that this combination therapy reverses diabetes and preserves the functional integrity of the transplanted stem cell-derived islets.

iTOL-100, an immunomodulatory microgel designed to eliminate the need for chronic systemic immunosuppression and shown to induce local immune acceptance of transplanted islets, was found to be compatible with stem cell-derived islets.

IsletRx, a preparation of human, stem cell-derived islets, is a scalable and virtually unlimited source of insulin-producing cells and could address the critical shortage of donor islets for transplantation.

The transplantation procedure is performed in a retrievable site, ensuring the possibility of graft retrieval through a minimally invasive surgery, if needed.

The study reports reversal of disease in a chemically induced model of diabetes, with comparable efficacy of IsletRx in the presence or absence of iTOL-100, indicating a lack of toxicity from the microgel.

iTolerance is pleased to co-sponsor the project at the Diabetes Research Institute toward a functional cure of T1D through the combination of human stem cell-derived insulin producing islet cells together with our iTOL-100 proprietary immunomodulator, said Anthony Japour, M.D., CEO of iTolerance, Inc. Removing the need for life-long toxic immunosuppressive agents in islet transplantation is a common goal among those working toward a cure for T1D through transplantation without immunosuppression.

Our collaboration with iTolerance opens an innovative and world-first avenue for transplanting pancreatic islet cells into people with diabetes without the need for full suppression of the immune system, which is required today in organ transplants, said Michel Revel, M.D., Ph.D., chief scientist at Kadimastem, Ltd. Our company produces high-quality pancreatic islet cells. The joint data collected by us proves the possibility of combining our cells with the material that locally prevents the rejection of the implant developed by our project partner iTolerance. Having successfully completed an Interact meeting with the FDA, the two companies are moving together to the pre-IND submission stage.

IsletRx is comprised of clinical-grade clusters of human pancreatic islet like cells (ILCs) with the ability to secrete insulin. IsletRx cells can detect the sugar levels in the body and produce the required amounts of insulin and glucagon. The companys technology can select and enrich only the highest functioning and purest islet cells from the population of pluripotent stem cells, which enables the maximum therapeutic effect.

The project was supported in part by iTolerance, Inc., Kadimastem, Ltd., grants funded by the Breakthrough T1D Foundation (formerly known as JDRF) and the Israel-U.S. Binational Industrial Research (BIRD) Foundation.

Tags: Camillo Ricordi, diabetes, Diabetes Research Institute, DRI, giacomo lanzoni, islet cell transplantation, pancreas

Original post:
Diabetes Research Institute Announces Breakthrough Transplantation Approach for the Treatment of Type 1 Diabetes ... - University of Miami

With its advanced algorithm that provides autocorrections every 5 minutes, the latest data demonstrated that the MiniMed 780G system decreased rates of early morning hyperglycemia, known asdawn phenomenon, and improved overnight sleep

DUBLIN and ORLANDO, Fla., June 21, 2024 /PRNewswire/ -- Medtronic plc(NYSE: MDT),a global leader in healthcare technology, is presenting a comprehensive body of new data at the American Diabetes Association's (ADA) 84thScientific Sessions that showcases the benefits of the MiniMed 780G system. New data shows how the system addresses hyperglycemia and nighttime burden, adding to the established body of evidence that demonstrates the system's ability to tackle unique and burdensome challenges of diabetes, such as managing highs and meal-time management or carb counting, while also mirroring outcomes across a wide-ranging patient population.

Tackling hyperglycemia to improve long-term health with type 1 diabetesAmong the burdens of living with diabetes, hyperglycemia can often be overshadowed by hypoglycemia. Yet, in the U.S., only 26% of people living with diabetes achieve HbA1c levels of <7.0%.1Reducing the time spent with high blood sugars continues to be a significant unmet need as it can lead to serious health problems impacting multiple organs.2 For children, prolonged highscan have adverse effects on memory, IQ, executivefunctioning, and learning.3

One cause of high blood sugars is the dawn phenomenon, an increase in glucose levels in the early morning.4 This can be a common occurrence for those living with diabetes and may add to feelings of frustration with diabetes. An encouraging new retrospective analysis of real-world data (n= 6026) showed that this morning peak was nearly eliminated for users who upgraded from the MiniMed 770G system to the MiniMed 780G system. The data assessed the elevation of sensor glucose levels >20 mg/dL from 3 - 6 a.m. compared to 12 3 a.m. at least 30% of the nights. The transition from the MiniMed 770G system to the MiniMed 780G system decreased dawn phenomenon rates from 12.2% to 4.5%. Time in Range also increased from 87.7% to 91.4% from 12 6 a.m., which is consistent with dawn phenomenon trends.

Early and consistent management of hyperglycemia is critical as it has protective effects on the body that can last for decades.5 "For those living with type 1 diabetes, dawn phenomenon can be a stressful occurrence that feels out of one's control," explained Robert Vigersky, MD, Chief Medical Officer, Medtronic Diabetes. "The introduction of the MiniMed 780G system has made it easier to maintain target glucose range with less effort to protect against hyperglycemia.6,7 It's been an absolute gift for my patients who have struggled with stubborn highs throughout their diabetes journey."

Reducing nighttime burden For individuals living with type 1 diabetes, CGM-generated alerts and the need to deliver manual boluses disrupt sleeping through the night adding to the burden of diabetes. The MiniMed 780G system is designed to reduce the burden of diabetes throughout the day and night. Additional real-world data from a retrospective analysis presented at ADA (n=8019; <7 y/o, previously on the MiniMed 770G system who had greater than 14 nights on both systems) demonstrated that users had fewer overnight sleep interruptions and Time in Range improvements as a result of the automatic adjustments in insulin and correction of glucose levels every 5 minutes, including during sleep. With the MiniMed 780G system, nighttime alerts decreased 45% for all users and 55% for those who used recommended optimal settings. Additionally, uninterrupted sleep, a greatly desired outcome for those living with diabetes, increased by 30 and 36 minutes per night, respectively. These results add to the diabetes burden reduction that MiniMed 780G system users experience with an advanced algorithm with frequent, every 5-minute autocorrections.

The continued evolution of the MiniMed 780G system to reduce burdenAlong with evidence on the currently available MiniMed 780G system, additional data will be presented on the next iteration of the system,* which aims to further reduce diabetes management burden through its design. The system is intended to be paired with the Simplera Sync sensor, a disposable, all-in-one continuous glucose monitor (CGM) designed to require no overtape.

A 24-site, single arm study evaluated the use of the next iteration of the MiniMed 780G system algorithm paired with the Simplera Sync sensor. Results were promising across all clinical outcomes metrics including Time in Range (TIR), Time in Tight Range (TITR) and Time Above Range (TAR), compared to the run-in group where hybrid closed loop (auto basal only) or open-loop delivery was used. The study included the use of recommended optimal settings (ROS) (100 mg/dL set target with an active insulin time of 2 hours) related to TIR, TITR, and TAR.

"The MiniMed 780G system has firmly established itself as a proven automated insulin delivery system," said study investigator Gregory Forlenza, MD, professor and pediatric endocrinologist at the Barbara Davis Center. "With the next iteration of the system and this next-generation Simplera Sync sensor, the overall experience for people living with type 1 diabetes could be enhanced and may prove to be a compelling option for diabetes management particularly when leveraged in combination with recommended optimal settings."

The MiniMed 780G system** is currently available for ages 7 and above in over 100 countries globally and will be launching with the Simplera Sync sensor in parts of Europe in late July. Currently, Simplera Sync is investigational and not approved for commercial use in the U.S.*

Safety and Glycemic Outcomes Using the MiniMed 780G system with an All-in-One Disposable Sensor with Transmitter 3-month study period (n=109, ages 7-17; n=107, ages 18-80)

Youths

(ages 7-17)

Adults

(ages 18-80)

Run-in (N=112)

Study (N=109)

ROS (N=41)

Run-in (N=110)

Study (N=107)

ROS (N=44)

Time in Smart Guard, %

14.531.3

93.511.3

96.93.1

33.240.3

96.66.6

97.53.7

Mean SG, mg/dL

180.427.1

154.417.6

149.015.3

161.018.7

142.212.8

136.512.0

Percentage of time spent at glucose ranges

<70 mg/dL

(% TBR)

1.61.7

1.91.4

1.91.2

1.71.9

1.51.4

1.71.4

70-140 mg/dL

(% TITR)

32.114.1

49.29.7

52.79.2

39.213.0

56.110.5

61.69.9

70-180 mg/dL

(% TIR)

54.415.7

71.49.9

74.79.3

66.512.6

80.28.1

83.87.4

>180 mg/dL

(% TAR)

44.016.1

26.710.1

23.39.4

31.813.1

18.28.4

14.57.7

Caption: Glycemic metrics and insulin delivered during youth and adult MiniMed 780G system investigational use with the disposable all-in-one Simplera Sync sensor

To view this data at the 84thAmerican Diabetes Association (ADA) Scientific Sessions inOrlando, Florida, view the company's previous announcement here for presentation times.

About MedtronicBold thinking. Bolder actions. We are Medtronic. Medtronic plc, headquartered in Dublin, Ireland, is the leading global healthcare technology company that boldly attacks the most challenging health problems facing humanity by searching out and finding solutions. Our Mission to alleviate pain, restore health, and extend life unites a global team of 95,000+ passionate people across more than 150 countries. Our technologies and therapies treat 70 health conditions and include cardiac devices, surgical robotics, insulin pumps, surgical tools, patient monitoring systems, and more. Powered by our diverse knowledge, insatiable curiosity, and desire to help all those who need it, we deliver innovative technologies that transform the lives of two people every second, every hour, every day. Expect more from us as we empower insight-driven care, experiences that put people first, and better outcomes for our world. In everything we do, we are engineering the extraordinary. For more information on Medtronic, visit http://www.Medtronic.com and follow Medtronic on LinkedIn.

About Medtronic Diabetes (www.medtronicdiabetes.com) Medtronic Diabetes is on a mission to alleviate the burden of diabetes by empowering individuals to live life on their terms, with the most advanced diabetes technology and always-on support when and how they need it. We've pioneered first-of-its-kind innovations for over 40 years and are committed to designing the future of diabetes management through next-generation sensors (CGM), intelligent dosing systems, and the power of data science and AI while always putting the customer experience at the forefront.

Any forward-looking statements are subject to risks and uncertainties such as those described in Medtronic's periodic reports on file with the Securities and Exchange Commission. Actual results may differ materially from anticipated results.

*Investigational. Not approved by the FDA for any use and not commercially available in the US.

**MiniMed 780G system is for type 1 ages 7 and over. Prescription required. WARNING: Do not use SmartGuard feature for people who require less than 8 units or more than 250 units of insulin/day. For details, seehttps://bit.ly/780gRisks

Refers to auto correct, which provides bolus assistance. Can deliver all auto correction doses automatically without user interaction, feature can be turned on and off.

Refers toSmartGuard feature. Individual results may vary.

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New MiniMed 780G system data demonstrates ability to address persistent blood sugar challenges for people with ... - PR Newswire

Gdask, Poland 24 June 2024 PolTREG S.A. (Warsaw Stock Exchange: PTG) , a clinical-stage biotechnology company developing cellular therapies for a range of autoimmune diseases, today announces that its polyclonal Treg cell therapy PTG-007 demonstrated significant insulin secretion restoration in early-onset type-1 diabetes (T1D) patients, as well as a longer period of disease remission compared to a control group receiving standard-of-care, in a long-term clinical study into the safety and efficacy of lead asset PTG-007. The study monitored pediatric patients who received the autologous treatment over a period of 7 to 12 years.

The main findings were:

This long-term study is a confirmation that the significant efficacy we found in our Phase 1/2 clinical trial for PTG-007 is sustainable over the long term. At PolTREG, we believe that PTG-007 has the potential to prevent type-1 diabetes, freeing patients of the life-long burden of having to take frequent insulin injections, and the serious long-term complications of the disease. The results of this study are an important step in that direction, said Prof Piotr Trzonkowski, Chief Executive Officer of PolTREG.

With the study, PolTREG has fulfilled a requirement by the European Medicines Agency to confirm the safety of Treg therapies at least 5 years after their administration. To the best of PolTREGs knowledge, no other company currently can show similar long-term safety results of Treg therapy in T1D. This is a significant competitive advantage, and paves the way for the company to launch a pivotal Phase 2/3 study of PTG-007 to treat T1D.

PolTREG is currently seeking partnership funding for this pivotal trial, the final step required before seeking regulatory authorization for commercialisation. The company will submit the data for a peer-reviewed scientific publication in the near future. Later this year, we will also be launching a Phase 2 study in presymptomatic patients, children who are not yet showing any symptoms but in whom we are now able to detect diabetes, Prof Trzonkowski said.

PolTREG holds one of the largest and most advanced pipelines for Treg therapies for autoimmune disease, developing both polyclonal and engineered therapies. Its lead candidate, PTG-007, an autologous polyclonal Treg treatment, is in mid-stage clinical studies for T1D and multiple sclerosis (MS). Next year, PolTREG expects to start a first-in-human trial of its engineered CAR-Tregs for treatment of two neurodegenerative diseases, MS and amyotrophic lateral sclerosis (ALS). The company also is in preclinical development with two further types of engineered Treg cells.

PolTREG manufactures all its Treg therapeutics at its own GMP-certified manufacturing facility. It is the first company in the world to administer Treg therapies to patients, and, under a hospital exemption valid in Poland, the first to start receiving revenues from a Treg therapeutic for autoimmune disease. Its GMP manufacturing facility is one of Europes largest and most advanced, boasting over 2,100 sqm of laboratory space, including 15 production lines. PolTREG has the option to substantially expand the facility to accommodate manufacturing of next-generation engineered therapies and cell therapies. It can ship its wide range of cellular therapy products across Europe within 24 hours.

About PolTREG PolTREG is a global leader in developing autoimmune therapies based on T-regulatory cells (Tregs). Its lead product, PTG-007, autologous Treg treatment for early-onset Type-1 Diabetes (T1D) is ready for Phase 2/3 clinical testing, for which the company is seeking a partnership. The company will launch Phase 2 trials for PTG-007 to treat Multiple Sclerosis (MS) in the second half of 2024, for RRMS and PPMS. PolTREG also has engineered Tregs, including CAR-Tregs, antigen-specific Tregs and TCR-Tregs, in the preclinical stage. PolTREG has completed four clinical trials with more than 100 patients treated with Tregs.

For more information please visit http://www.poltreg.com.

PolTREG S.A. Prof Piotr Trzonkowski Chief Executive Officer ir@poltreg.com +48 512 532 401

Media Relations Douwe Miedema Cohesion Bureau +352 621 562 764 douwe.miedema@cohesionbureau.com

Important information The contents of this announcement include statements that are, or may be deemed to be, "forward-looking statements". These forward-looking statements can be identified by the use of forward-looking terminology, including the words "believes", "estimates," "anticipates", "expects", "intends", "may", "will", "plans", "continue", "ongoing", "potential", "predict", "project", "target", "seek" or "should", and include statements the Company makes concerning the intended results of its strategy. By their nature, forward-looking statements involve risks and uncertainties and readers are cautioned that any such forward-looking statements are not guarantees of future performance. The company's actual results may differ materially from those predicted by the forward-looking statements. The company undertakes no obligation to publicly update or revise forward-looking statements, except as may be required by law.

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PolTREG's type-1 diabetes Treg cell therapy PTG-007 - GlobeNewswire

Tzield (teplizumab) was approved in2022, becoming the first treatment to delay the onset of type 1 diabetes. Currently, Tzield is for people aged 8 and up who have stage 2type 1 diabetes meaning they have two or more autoantibodies and abnormal blood sugar, but not high enough to be stage 3 which means the person already has type 1 diabetes.

What if Tzield could be used later on, once someone has been diagnosed with diabetes, to prevent progression of the disease?

Since Tzields approval, researchers like Dr. Kevan Herold, professor of immunobiology and of medicine and an endocrinologist at Yale University, have begun testing the medication for different stages of type 1 diabetes. Indeed, previousresearch by Herold and colleagues has suggested that Tzield might preserve beta cells.

If Tzield is able to prevent progression in those with newly diagnosed diabetes, it could potentially be a big improvement. For instance, this could lead to lower insulin or no insulin , meaning fewer or no injections and a lower risk ofhypoglycemia (low blood sugar). Its possible this could even translate to longer-term benefits, such as a lower risk ofdiabetes complications.

Tzield works by attaching to and modifying T-cells, a type of immune cells that destroy the insulin-producing beta cells in type 1 diabetes. In doing so, Tzield helps interrupt the immune systems attack on beta cells and delayed the onset of type 1 diabetes in a clinical trial by two to three years.

ThePROTECT study investigated whether treatment with Tzield could prevent disease progression in people newly diagnosed with type 1 diabetes. The study included 328 children and teens, ages 8 to 17 years old, who had been diagnosed with diabetes for up to 6 weeks. Participants were randomly assigned to receive two courses of Tzield treatment or a placebo.

In the original PROTECT trial, researchers found that Tzield led to significantly greater preservation of beta cells compared to placebo.

The problem, Herold said, was that the PROTECT study was done during theCovid-19 pandemic, which threw a wrench into the conduct of the trial. As a result of the pandemic, some participants were unable to receive a full course of Tzield.

Thecurrent analysis specifically looked at participants who strictly followed the treatment protocol, meaning that they received 80% or more of the prescribed dose of Tzield. Participants who received less than 80% of the recommended dose, took prohibited medications (such as steroids or vaccines), or became pregnant were not included in this analysis.

To measure how well Tzield preserved beta cells, the researchers looked at a metric called C-peptide. C-peptide is made by beta cells during insulin production and is found in blood or urine tests. C-peptide is commonly used in studies of type 1 diabetes, such as in research investigating the cell therapy Lantidra and Vertexs VX-880 stem cell treatment. A higher C-peptide level indicates that more beta cells are working and producing insulin.

This analysis included 275 participants: 180 were randomly assigned to receive Tzield, and 95 were randomly assigned to the placebo. At the start of the study, participants had an average age of 12, BMI of 19, and an A1C of 9%.

At week 78:

Despite these findings, A1C levels were comparable between the Tzield and placebo groups.

An additional analysis found that timing of the second course of Tzield whether participants received it at 6 months as recommended, or at 12 months did not affect preservation of beta cells, Herold noted. This is an encouraging finding, as it suggests participants whose dosing was interrupted by the pandemic were still able to reap the benefits of Tzield.

This analysis of the PROTECT study showed that participants who received Tzield as directed had significantly greater beta cell preservation and time in range. Participants treated with Tzield also had lower insulin needs, which may have contributed to the lower risk of severe hypoglycemia.

These findings suggest that Tzield may be useful in preventing progression of type 1 diabetes in those newly diagnosed with the condition. Note that this study only investigated children and teens, so more research is needed, including whether Tzield is beneficial for the growing population of adults newly diagnosed with type 1 diabetes.

Overall, this analysis suggests that Tzield may be beneficial across a wider time frame not just in stage 2 type 1 diabetes. Hopefully, future research will determine the best time for participants to receive Tzield.

I think the general impression at this point is that theres probably a window of treatment opportunity that is sometime around the rapid decline in beta cell function that occurs in the peri-diagnosis period, Herold said.

Learn more about new treatments for type 1 diabetes:

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Could Tzield Help Children Newly Diagnosed with Diabetes? - diaTribe Foundation

The FreeStyle Libre 3 continuous glucose monitor. [Image courtesy of Abbott] The Diabetes business unit at Abbott (NYSE:ABT) has gotten off to a hot start in 2024, with some significant developments on the CGM front.

With the recent FDA clearance of two over-the-counter sensors following significant automated insulin pump integrations, 2024 has been full of good news for the company.

Speaking toDrug Delivery Business News at the American Diabetes Association Scientific Sessions in Orlando, Florida, Abbott Diabetes SVP of Commercial Operations, Chris Scoggins, said the company wants to keep that momentum going.

2024 is shaping up to be an exciting year, a good year, Scoggins said. The excitement for us, at least in the U.S., is that were just pushing deeper and deeper into this really big, underserved patient population of people with type 2 diabetes.

As Abbott broadens its patient population, Scoggins said the company is reaching new channels, like primary care, benefitting more people with diabetes, namely type 2. He called it a new chapter in the brand.

Scoggins said the push for the type 2 population is an energizing endeavor.

Something thats important for everbody to understand is, we have much work to do as an industry to really bring to the type 2 population the technologies and brands that are pretty well covered and supplied into that smaller type 1 population, Scoggins explained. Its something that puts a lot of wind in our sails.

Abbott hears patient stories often, he said, highlighting how they benefit from using the FreeStyle Libre CGM platform. According to Scoggins, it helps them see things for the first time that perhaps they failed to understand before.

Using minute-by-minute glucose readings and seeing how lifestyle choices, food choices or activity impacts glucose variability provides things that were previously hidden in a 90-day HbA1c test.

You cant really see that type of variability, Scoggins said. But, when youre doing daily time in range, all of a sudden, those lifestyle choices become very real. Those are the kinds of learnings and insights that the type 2 population can really derive benefit from when using Libre.

At the start of the year, Abbott made great strides in automated insulin delivery, pairing its FreeStyle Libre 2 Plus with Insulets Omnipod 5 in Europe and announcing compatibility with the Tandem Diabetes Care t:slim X2 system in January.

Its a really important segment, Scoggins said. Theres a high medical need for people that have type 1 diabetes and use a pump.

Globally, he explained, more than half a billion people have diabetes. The vast majority fall into the type 2 category, Scoggins said. With FreeStyle Libre, he says Abbott wanted to think about the largest groups of people underserved by diabetes technology. With the push for addressing the type 2 population taking the front seat, the company has now turned some focus toward the type 1 subgroup targeted by automated insulin delivery technology makers.

Now, Scoggins says, its important that Abbott gets it right with regard to automated insulin delivery.

Right now, the company offers the FreeStyle Libre 2 plus, built on the Libre 2 platform, in the U.S. with Tandem. However, it actually started pump connectivity with Libre 3, the latest generation, in Europe, with Ypsomed and CamDiab.

Scoggins said the company feels strongly about the process of working with a pump partner to create an effectively connected, quality, regulated system that everyone feels good about, both for regulatory and technological reasons. Ultimately, the company intends to continue expanding the options for this patient base.

Were going to help the patients we serve and engender the confidence of the endocrinologist, so you know to trust Libre to connect to a pump, Scoggins explained. While we are showing up in the pump space later than some of our competitors, our intent is to not just show up, but to become the brand of choice and the standard of care.

We dont want to just show up and participate. We want to be the reference.

The launch of Lingo effectively a CGM for monitoring health and wellness outside diabetes widens the population Abbott can reach, but, in a diabetes-specific sense, the over-the-counter Libre Rio is yet another major step forward in reaching more patients.

Libre Rio provides monitoring for adults with type 2 diabetes who arent on insulin and manage diabetes through lifestyle modifications. Like the companies prescription CGMs, Libre Riowill rival Dexcoms OTC Stelo for people with type 2 diabetes who do not use insulin.

Theres not a one-product-serves-all solution that we could see meet the needs in the market, Scoggins said. Thats why we offered to separate sensors to serve both of these consumers.

As a research-driven organization, Scoggins says Abbott is always looking to build upon its platforms, like with Rio and Lingo.DVP, Technical Operations, Marc Taub, explained this innovation process last fall at DeviceTalks West.The company also continues development on afirst-of-its kind, all-in-one sensor that measures both glucose and ketone.

Scoggins said the company has been somewhat surprised by the reaction of the medical community and the interest in understanding how that sensor could help people at risk for diabetic ketoacidosis (DKA).

Abbott built this sensor on the Libre 3 form factor. Scoggins said it fits with what FreeStyle Libre stands for, providing functional understanding of the variability of glucose but also visibility into the risk of ketosis. It also improves upon the existing ketone strip which Abbott offers with low utilization of that product. The convenience of having that second measure included in a glucose sensor could set the device apart.

Still in development and not at the stage of commercial discussions yet, the sensor still could garner plenty of attention. Scoggins expects rigorous clinical activity to prepare for regulatory submission and more to come on this front.

More can benefit and that interest in the multi-analyte sensor, I think its just kind of scratching the surface, Scoggins said. Theres so much more we can do.

More here:
Abbott targets type 2 diabetes with 'exciting year' ahead - Drug Delivery Business News